Original Article
Subject Category: Immunology/Infection
Journal of Investigative Dermatology (2008) 128, 1719–1727; doi:10.1038/jid.2008.5; published online 31 January 2008
Cutaneous Hypersensitivities to Hapten Are Controlled by IFN-
-Upregulated Keratinocyte Th1 Chemokines and IFN-
-Downregulated Langerhans Cell Th2 Chemokines
Tomoko Mori1, Kenji Kabashima1, Ryutaro Yoshiki1, Kazunari Sugita1, Noriko Shiraishi1, Ayako Onoue1, Etsushi Kuroda2, Miwa Kobayashi1, Uki Yamashita2 and Yoshiki Tokura1
- 1Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan
- 2Department of Immunology, University of Occupational and Environmental Health, Kitakyushu, Japan
Correspondence: Dr Tomoko Mori, Department of Dermatology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu 807-8555, Japan. E-mail: cdm63280@par.odn.ne.jp
Received 15 August 2007; Revised 11 December 2007; Accepted 12 December 2007; Published online 31 January 2008.
Abstract
There are immediate, late-phase, and delayed-type reactions to exogenous agents. In IFN-
-knockout (IFN-
-
/-
) and wild-type B6 mice, we examined the response to picryl chloride (PCl) for assessing delayed-type reactions, and the responses to repeatedly challenged FITC for immediate and late-phase reactions. The delayed-type hypersensitivity was depressed in IFN-
-
/-
mice, and the immediate and late-phase reactions were enhanced in IFN-
-
/-
mice. As skin-infiltrating lymphocytes were scarce at the PCl-challenged site of IFN-
-
/-
mice, we investigated chemokine production by keratinocytes and Langerhans cells (LCs). A real-time PCR analysis demonstrated that Th1 chemokines (CXCL9 and CXCL10) and Th2 chemokines (CCL17 and CCL22) were derived mainly from keratinocytes and LCs, respectively. Challenge with PCl or FITC augmented keratinocyte expression of Th1 chemokines in wild-type but not in IFN-
-
/-
mice, and Th2 chemokine production by LCs was induced by repeated FITC in IFN-
-
/-
mice. Finally, transfer of carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled draining lymph node cells from hapten-sensitized B6 mice or lymph node cells from sensitized green fluorescent protein (GFP) mice to naive IFN-
-
/-
mice revealed less infiltration of CFSE+ or GFP+ lymphocytes at the challenged site. Our study suggests that one of the crucial actions of IFN-
is upregulation of keratinocyte production of Th1 chemokines and downregulation of LC production of Th2 chemokines.
Abbreviations:
B6, C57BL/6J; CFSE, carboxyfluorescein diacetate succinimidyl ester; CHS, contact hypersensitivity; Ct, cycle threshold; DTH, delayed-type hypersensitivity; EC, epidermal cell; GFP, green fluorescent protein; IFN-
-
/-
, IFN-
-knockout; LC, Langerhans cell; PCl, picryl chloride
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